The symptoms of Space Motion Sickness (SMS) include an inability to appraise and filter out unwanted stimuli, a process that can lead to a sensory gating deficit, which is exhibited in other neurologic disorders, all of which are marked by dysregulation of the reticular activating system (RAS). Our preliminary work with patients suffering from balance disorders and tinnitus indicates the presence of a similar cognitive impairment. We have investigated countermeasures for SMS using a rotation/CNS assessment paradigm that involves overstimulation of the semicircular canals with a rotary chair. Using our CNS assessment to pinpoint the level of the neuraxis most affected by rotation, targeted therapies can be evaluated for their ability to restore a) arousal and habituation (sensory gating) functions (as determined by measures of the P50 potential), b) attentional components of reaction time (using a Psychomotor Vigilance Task [PVT]), c) cognition and memory (using an Operant Test Battery [OTB]), and higher cognitive function and critical judgment (using Near Infrared Spectroscopy [NIRS]). We have shown that rotation leads to decreased habituation to repetitive stimuli, which may be at the root of the sensory gating deficit seen in SMS, and that scopolamine is the drug of choice for treating SMS; however, drug delivery parameters need to be optimized to effectively counteract the CNS deficits due to rotation. Our overall goal is to develop and implement a comprehensive assessment of all levels of the neuraxis in an effort to determine CNS deficits due to a provoked (e.g. rotation) or existing condition (e.g. balance disorder, tinnitus), and develop and assess strategies to restore those deficits. We hypothesize that by localizing the level of the neuraxis affected by a provoked or existing condition, targeted therapies can be applied that will alleviate the cognitive deficits, even if the existing condition is not eliminated. In Aim 1 we will establish the validity of our proposed paradigm for evaluating and isolating specific CNS effects due to a provoked condition (rotation). In Aim 2 we will localize the cognitive impairment in patients with chronic balance disturbances to design optimal therapeutic strategies for these individuals. In Aim 3 we will examine the impact of tinnitus on all levels of the neuraxis in an effort to apply targeted therapy to patients with this diagnostic entity. We will be able to pursue future directions with the translational component of our research by applying our CNS assessment to other clinical entities (Meniere's disease, poorly compensated vestibular neuronitis, post-concussion balance syndrome, multisensory disorder) and assessing outcomes after treatment.